Background: Pre-operative 5-Fu based chemoradiation is still the standard of treatment for locally advanced rectal cancer (LARC). Although local recurrence rate had been controlled, about 30% of patients will develop distant metastases, which is the main obstacle for improving survival of LARC. Besides, preoperative radiation causes lots of concerns about anal and sexual functions. Whether systemic chemotherapy alone is effective enough in treating rectal cancer is not yet known. In our previous study of neoadjuvant mFOLFOX6 with or without radiotherapy in LARC, about 30% of patients in the arm with chemotherapy alone showed good response. And FOLFOXIRI had showed higher response rate in metastatic colorectal cancer. This phase II study is to explore whether pre-operative FOLFOXIRI could further improve the ratio of tumor downstaging (ypT0-2N0) in LARC. Methods: The primary endpoint is the ratio of tumor downstaging to ypT0-2N0M0 (pCR and stage I).The secondary endpoint included pathologic complete response rate, 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that FOLFOXIRI could improve the downstaging rate from 30% to 50% with 5% type I error and 80% power. 84 patients met inclusion criteria will be enrolled in the trial. All patients will receive the study regimen every 2 weeks for 4-6 cycles. MRI of the pelvic will be performed every 2 cycles of the therapy to assess clinical response. If the tumor response over 20% after 4 cycles of treatment, the patient will go to surgery (TME) directly or 2 more cycles of treatment before surgery under the decision of MDT. On the contrary, if the tumor show poor response (< 20%), short-term radiotherapy will be performed before operation. After surgery, 6-8 cycles of mFOLFOX6 will be given as adjuvant chemotherapy. Clinical trial information: NCT02217020 Clinical trial information: NCT02217020